chr17-80628572-A-C

Variant names:

• chr17-80628572-A-C
• rs8071015
• NM_020761.3:c.265+2779A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.265+2779A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,388 control chromosomes in the GnomAD database, including 6,712 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6712 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615
• Publications: 6 publications found

Genes affected

RPTOR (HGNC:30287): (regulatory associated protein of MTOR complex 1) This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.265+2779A>C		intron_variant	Intron 2 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.265+2779A>C		intron_variant	Intron 2 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.265+2779A>C		intron_variant	Intron 2 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44754 AN: 151278 Hom.: 6709 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.323

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.296 AC: 44767 AN: 151388 Hom.: 6712 Cov.: 32 AF XY: 0.296 AC XY: 21932 AN XY: 73992

African (AFR) AF: 0.295 AC: 12160 AN: 41266

American (AMR) AF: 0.234 AC: 3568 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1366 AN: 5148

South Asian (SAS) AF: 0.267 AC: 1281 AN: 4792

European-Finnish (FIN) AF: 0.336 AC: 3484 AN: 10364

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20364 AN: 67820

Other (OTH) AF: 0.325 AC: 683 AN: 2104

Alfa AF: 0.276 Hom.: 3174

Bravo AF: 0.290

Asia WGS AF: 0.278 AC: 965 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.75
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8071015; hg19: chr17-78602372;